Autocrine vitamin D signaling switches off pro-inflammatory programs of TH1 cells.

The molecular mechanisms governing orderly shutdown and retraction of CD4+ type 1 helper T (TH1) cell responses remain poorly understood. Here we show that complement triggers contraction of TH1 responses by inducing intrinsic expression of the vitamin D (VitD) receptor and the VitD-activating enzyme CYP27B1, permitting T cells to both activate and respond to VitD. VitD then initiated the transition from pro-inflammatory interferon-γ+ TH1 cells to suppressive interleukin-10+ cells. This process was primed by dynamic changes in the epigenetic landscape of CD4+ T cells, generating super-enhancers and recruiting several transcription factors, notably c-JUN, STAT3 and BACH2, which together with VitD receptor shaped the transcriptional response to VitD. Accordingly, VitD did not induce interleukin-10 expression in cells with dysfunctional BACH2 or STAT3. Bronchoalveolar lavage fluid CD4+ T cells of patients with COVID-19 were TH1-skewed and showed de-repression of genes downregulated by VitD, from either lack of substrate (VitD deficiency) and/or abnormal regulation of this system.

The γδTCR combines innate immunity with adaptive immunity by utilizing spatially distinct regions for agonist selection and antigen responsiveness.

T lymphocytes expressing γδ T cell antigen receptors (TCRs) comprise evolutionarily conserved cells with paradoxical features. On the one hand, clonally expanded γδ T cells with unique specificities typify adaptive immunity. Conversely, large compartments of γδTCR+ intraepithelial lymphocytes (γδ IELs) exhibit limited TCR diversity and effect rapid, innate-like tissue surveillance. The development of several γδ IEL compartments depends on epithelial expression of genes encoding butyrophilin-like (Btnl (mouse) or BTNL (human)) members of the B7 superfamily of T cell co-stimulators. Here we found that responsiveness to Btnl or BTNL proteins was mediated by germline-encoded motifs within the cognate TCR variable γ-chains (Vγ chains) of mouse and human γδ IELs. This was in contrast to diverse antigen recognition by clonally restricted complementarity-determining regions CDR1-CDR3 of the same γδTCRs. Hence, the γδTCR intrinsically combines innate immunity and adaptive immunity by using spatially distinct regions to discriminate non-clonal agonist-selecting elements from clone-specific ligands. The broader implications for antigen-receptor biology are considered.

Defective STAT5 Activation and Aberrant Expression of BCL6 in Naive CD4 T Cells Enhances Follicular Th Cell-like Differentiation in Patients with Granulomatosis with Polyangiitis.

Granulomatosis with polyangiitis (GPA) is a potentially fatal small vessel vasculitis of unknown etiology, characterized by anti-neutrophil cytoplasmic autoantibodies, chronic inflammation, and granulomatous tissue damage. T cell dysregulation, comprising decreased regulatory T cell function and increased circulating effector memory follicular Th cells (TFH), is strongly associated with disease pathogenesis, but the mechanisms driving these observations are unknown. We undertook transcriptomic and functional analysis of naive CD4 T cells from patients with GPA to identify underlying functional defects that could manifest in the pathogenic profiles observed in GPA. Gene expression studies revealed a dysregulation of the IL-2 receptor ß/JAK-STAT signaling pathway and higher expression of BCL6 and BCL6-regulated genes in GPA naive CD4 T cells. IL-2-induced STAT5 activation in GPA naive CD4 T cells was decreased, whereas STAT3 activation by IL-6 and IL-2 was unperturbed. Consistently, BCL6 expression was sustained following T cell activation of GPA naive CD4 T cells and in vitro TFH differentiation of these cells resulted in significant increases in the production TFH-related cytokines IL-21 and IL-6. Thus, naive CD4 T cells are dysregulated in patients with GPA, resulting from an imbalance in signaling equilibrium and transcriptional changes that drives the skewed pathogenic CD4 effector immune response in GPA.

The Changing Face of Childhood Intussusception: A Refinement in the Technique of Saline Reduction and Outcome.

Aims: Intussusception is a common pediatric surgical emergency and an indicator for primary healthcare. We report our experience with childhood intussusception at a tertiary care hospital in the private sector in Central Kerala and add our refinement to the technique of hydrostatic saline reduction which had more desirable outcome. Settings and Design: Children presenting with the diagnosis of intussusception which were managed in our department of pediatric surgery at a private hospital in Kerala, India. Subjects and Methods: Eighty children, up to 15 years of age, (43 boys, 37 girls) confirmed to have intussusception on ultrasound and managed in our institution from October 2016 to July 2020 with hydrostatic saline reduction. Sixty-two (77%) of them were aged 3 months to 3 years (numbers <10 to be written in words); the age of idiopathic intussusception. Statistical Analysis Used: SPSS V25. Association between variables using Chi square test and independent t test. Results: A total of 80 children met the criteria out of that (n = 79) had successful nonoperative reduction. Hydrostatic saline enema 73, One Barium and five air enema. A child presented in shock was taken up for laparotomy and reduced operatively. Six recurred within 24 h (7% early recurrence) and a second attempt at nonoperative reduction succeeded in all six of them. (numbers <10 in words). Eleven children (14%) had a late recurrence, the attempt at saline hydrostatic reduction was successful in only 3 (27%) and 8 went on to have surgery. Six were successfully reduced operatively and 2 had resection anastomosis. Conclusions: After excluding those who need surgery on clinical grounds, we report a 98.7% success with nonoperative reduction for the first instance of intussusception, a 24 h recurrence of 7%, with successful repeat reductions in all. With the refinement in the technique, we could achieve a desirable outcome. At the first presentation, surgery was indicated in 1 of the 80 children. We report a late recurrence rate of 14%, with a 27% success rate for nonoperative reduction. No pathological lead points were identified even in this group. All the children had an uneventful and a faster recovery. In our series, we had 97.5% follow-up rate.

Changes in endogenous abscisic acid and stomata of the resurrection fern, Pleopeltis polypodioides, in response to de- and rehydration.

PREMISE: While angiosperms respond uniformly to abscisic acid (ABA) by stomatal closure, the response of ferns to ABA is ambiguous. We evaluated the effect of endogenous ABA, hydrogen peroxide (H2 O2 ), nitric oxide (NO), and Ca2+ , low and high light intensities, and blue light (BL) on stomatal opening of Pleopeltis polypodioides. METHODS: Endogenous ABA was quantified using gas chromatography-mass spectrometry; microscopy results and stomatal responses to light and chemical treatments were analyzed with Image J. RESULTS: The ABA content increases during initial dehydration, peaks at 15 h and then decreases to one fourth of the ABA content of hydrated fronds. Following rehydration, ABA content increases within 24 h to the level of hydrated tissue. The stomatal aperture opens under BL and remains open even in the presence of ABA. Closure was strongly affected by BL, NO, and Ca2+ , regardless of ABA, H2 O2 effect was weak. CONCLUSIONS: The decrease in the ABA content during extended dehydration and insensitivity of the stomata to ABA suggests that the drought tolerance mechanism of Pleopeltis polypodioides is independent of ABA.

The Management of Children and Youth With Pediatric Mental and Behavioral Health Emergencies.

Mental and behavioral health (MBH) emergencies in children and youth continue to increasingly affect not only the emergency department (ED), but the entire spectrum of emergency medical services for children, from prehospital services to the community. Inadequate community and institutional infrastructure to care for children and youth with MBH conditions makes the ED an essential part of the health care safety net for these patients. As a result, an increasing number of children and youth are referred to the ED for evaluation of a broad spectrum of MBH emergencies, from depression and suicidality to disruptive and aggressive behavior. However, challenges in providing optimal care to these patients include lack of personnel, capacity, and infrastructure, challenges with timely access to a mental health professional, the nature of a busy ED environment, and paucity of outpatient post-ED discharge resources. These factors contribute to prolonged ED stays and boarding, which negatively affects patient care and ED operations. Strategies to improve care for MBH emergencies, including systems level coordination of care, is therefore essential. The goal of this policy statement and its companion technical report is to highlight strategies, resources, and recommendations for improving emergency care delivery for pediatric MBH.

Immunogenomics of Colorectal Cancer Response to Checkpoint Blockade: Analysis of the KEYNOTE 177 Trial and Validation Cohorts.

BACKGROUND & AIMS: Colorectal cancer (CRC) shows variable response to immune checkpoint blockade, which can only partially be explained by high tumor mutational burden (TMB). We conducted an integrated study of the cancer tissue and associated tumor microenvironment (TME) from patients treated with pembrolizumab (KEYNOTE 177 clinical trial) or nivolumab to dissect the cellular and molecular determinants of response to anti- programmed cell death 1 (PD1) immunotherapy. METHODS: We selected multiple regions per tumor showing variable T-cell infiltration for a total of 738 regions from 29 patients, divided into discovery and validation cohorts. We performed multiregional whole-exome and RNA sequencing of the tumor cells and integrated these with T-cell receptor sequencing, high-dimensional imaging mass cytometry, detection of programmed death-ligand 1 (PDL1) interaction in situ, multiplexed immunofluorescence, and computational spatial analysis of the TME. RESULTS: In hypermutated CRCs, response to anti-PD1 immunotherapy was not associated with TMB but with high clonality of immunogenic mutations, clonally expanded T cells, low activation of Wnt signaling, deregulation of the interferon gamma pathway, and active immune escape mechanisms. Responsive hypermutated CRCs were also rich in cytotoxic and proliferating PD1+CD8 T cells interacting with PDL1+ antigen-presenting macrophages. CONCLUSIONS: Our study clarified the limits of TMB as a predictor of response of CRC to anti-PD1 immunotherapy. It identified a population of antigen-presenting macrophages interacting with CD8 T cells that consistently segregate with response. We therefore concluded that anti-PD1 agents release the PD1-PDL1 interaction between CD8 T cells and macrophages to promote cytotoxic antitumor activity.

Association of Accuracy, Conclusions, and Reporting Completeness With Acceptance by Radiology Conferences and Journals.

BACKGROUND: Preferential publication of studies with positive findings can lead to overestimation of diagnostic test accuracy (i.e. publication bias). Understanding the contribution of the editorial process to publication bias could inform interventions to optimize the evidence guiding clinical decisions. PURPOSE/HYPOTHESIS: To evaluate whether accuracy estimates, abstract conclusion positivity, and completeness of abstract reporting are associated with acceptance to radiology conferences and journals. STUDY TYPE: Meta-research. POPULATION: Abstracts submitted to radiology conferences (European Society of Gastrointestinal and Abdominal Radiology (ESGAR) and International Society for Magnetic Resonance in Medicine (ISMRM)) from 2008 to 2018 and manuscripts submitted to radiology journals (Radiology, Journal of Magnetic Resonance Imaging [JMRI]) from 2017 to 2018. Primary clinical studies evaluating sensitivity and specificity of a diagnostic imaging test in humans with available editorial decisions were included. ASSESSMENT: Primary variables (Youden's index [YI > 0.8 vs. <0.8], abstract conclusion positivity [positive vs. neutral/negative], number of reported items on the Standards for Reporting of Diagnostic Accuracy Studies [STARD] for Abstract guideline) and confounding variables (prospective vs. retrospective/unreported, sample size, study duration, interobserver agreement assessment, subspecialty, modality) were extracted. STATISTICAL TESTS: Multivariable logistic regression to obtain adjusted odds ratio (OR) as a measure of the association between the primary variables and acceptance by radiology conferences and journals; 95% confidence intervals (CIs) and P-values were obtained; the threshold for statistical significance was P < 0.05. RESULTS: A total of 1000 conference abstracts (500 ESGAR and 500 ISMRM) and 1000 journal manuscripts (505 Radiology and 495 JMRI) were included. Conference abstract acceptance was not significantly associated with YI (adjusted OR = 0.97 for YI > 0.8; CI = 0.70-1.35), conclusion positivity (OR = 1.21 for positive conclusions; CI = 0.75-1.90) or STARD for Abstracts adherence (OR = 0.96 per unit increase in reported items; CI = 0.82-1.18). Manuscripts with positive abstract conclusions were less likely to be accepted by radiology journals (OR = 0.45; CI = 0.24-0.86), while YI (OR = 0.85; CI = 0.56-1.29) and STARD for Abstracts adherence (OR = 1.06; CI = 0.87-1.30) showed no significant association. Positive conclusions were present in 86.7% of submitted conference abstracts and 90.2% of journal manuscripts. DATA CONCLUSION: Diagnostic test accuracy studies with positive findings were not preferentially accepted by the evaluated radiology conferences or journals. EVIDENCE LEVEL: 3 TECHNICAL EFFICACY: Stage 2.

Acceptance and results of therapy with omalizumab in real world Kerala setting: reports from the ARTWORK study, Kerala, South India.

OBJECTIVE: Despite the availability of effective medications, only a minority of asthma patients achieve guideline defined asthma control. Treatment success depends on patient concurrence to the prescribed drug and adherence to treatment. It is therefore crucial to identify the patient preferences as well as attitudes towards asthma medications. Omalizumab is recommended as a preferred option in step 5 of asthma therapy. There have been few studies to address patient perspectives on omalizumab therapy in India. METHODS: This was a retrospective study. Patients with inadequate asthma control were considered for the study. Systematic evaluation was done to identify and correct modifiable factors that can worsen asthma control. Patients with persisting poor asthma control who were deemed suitable to receive this agent were evaluated with their attitudes toward acceptance or refusal and the reasons for opting out were noted. The patients who received omalizumab were followed up to determine the results of treatment and duration of adherence to therapy. RESULTS: Thirty-five patients out of 51 patients chose to avoid this drug. The reasons for opting out included erroneous perception of optimal asthma control, cost of therapy, and concern about adverse effects. Patients took omalizumab for a median duration of 6 months. Improved asthma control and decreased frequency of exacerbation was noted in all patients which persisted during the 6-month follow-up. CONCLUSIONS: The majority of patients needing step 5 therapy opt out of omalizumab. Cost of drug, duration of therapy and erroneous perception of good asthma control account for refusing treatment. Omalizumab affords excellent clinical benefits to patients who receive it, and the benefits extend beyond the duration of therapy.

Incidence of cardiotoxicity and validation of the Heart Failure Association-International Cardio-Oncology Society risk stratification tool in patients treated with trastuzumab for HER2-positive early breast cancer.

PURPOSE: Trastuzumab improves survival in patients with HER2+ early breast cancer. However, cardiotoxicity remains a concern, particularly in the curative setting, and there are limited data on its incidence outside of clinical trials. We retrospectively evaluated the cardiotoxicity rates [left ventricular ejection fraction (LVEF) decline, congestive heart failure (CHF), cardiac death or trastuzumab discontinuation] and assessed the performance of a proposed model to predict cardiotoxicity in routine clinical practice. METHODS: Patients receiving curative trastuzumab between 2011 and 2018 were identified. Demographics, treatments, assessments and toxicities were recorded. Fisher's exact test, Chi-squared and logistic regression were used. RESULTS: 931 patients were included in the analysis. Median age was 54 years (range 24-83) and Charlson comorbidity index 0 (0-6), with 195 patients (20.9%) aged 65 or older. 228 (24.5%) were smokers. Anthracyclines were given in 608 (65.3%). Median number of trastuzumab doses was 18 (1-18). The HFA-ICOS cardiovascular risk was low in 401 patients (43.1%), medium in 454 (48.8%), high in 70 (7.5%) and very high in 6 (0.6%). Overall, 155 (16.6%) patients experienced cardiotoxicity: LVEF decline ≥ 10% in 141 (15.1%), falling below 50% in 55 (5.9%), CHF NYHA class II in 42 (4.5%) and class III-IV in 5 (0.5%) and discontinuation due to cardiac reasons in 35 (3.8%). No deaths were observed. Cardiotoxicity rates increased with HFA-ICOS score (14.0% low, 16.7% medium, 30.3% high/very high; p = 0.002). CONCLUSIONS: Cardiotoxicity was relatively common (16.6%), but symptomatic heart failure on trastuzumab was rare in our cohort. The HFA-ICOS score identifies patients at high risk of cardiotoxicity.

The RSNA International COVID-19 Open Radiology Database (RICORD).

The coronavirus disease 2019 (COVID-19) pandemic is a global health care emergency. Although reverse-transcription polymerase chain reaction testing is the reference standard method to identify patients with COVID-19 infection, chest radiography and CT play a vital role in the detection and management of these patients. Prediction models for COVID-19 imaging are rapidly being developed to support medical decision making. However, inadequate availability of a diverse annotated data set has limited the performance and generalizability of existing models. To address this unmet need, the RSNA and Society of Thoracic Radiology collaborated to develop the RSNA International COVID-19 Open Radiology Database (RICORD). This database is the first multi-institutional, multinational, expert-annotated COVID-19 imaging data set. It is made freely available to the machine learning community as a research and educational resource for COVID-19 chest imaging. Pixel-level volumetric segmentation with clinical annotations was performed by thoracic radiology subspecialists for all COVID-19-positive thoracic CT scans. The labeling schema was coordinated with other international consensus panels and COVID-19 data annotation efforts, the European Society of Medical Imaging Informatics, the American College of Radiology, and the American Association of Physicists in Medicine. Study-level COVID-19 classification labels for chest radiographs were annotated by three radiologists, with majority vote adjudication by board-certified radiologists. RICORD consists of 240 thoracic CT scans and 1000 chest radiographs contributed from four international sites. It is anticipated that RICORD will ideally lead to prediction models that can demonstrate sustained performance across populations and health care systems.

Percutaneous Image-Guided Biopsy of the Spleen: Experience at a Single Tertiary Care Center.

PURPOSE: The purpose of this study is to assess the complication rate of percutaneous image-guided biopsy of the spleen at our institution and to evaluate for variables associated with complication rate. METHODS: This is a Research Ethics Board approved retrospective study of consecutive patients who underwent image-guided biopsy of the spleen at our institution from January 2010 to November 2019. Complications, imaging findings, and pathologic diagnosis were reviewed. Complications (major and minor) were classified per Society of Interventional Radiology Guidelines, and complication rate was calculated. Logistic regression was applied to determine factors associated with complications. Diagnostic yield was calculated. RESULTS: In all, 55 patients (28 female) underwent splenic biopsy using ultrasound guidance. The most common indication was possible lymphoma in 41 (71.7%) patients followed by query metastasis 18 (31.5%) patients. Core biopsies (18 g/20 g) were done in 53 (92%) cases, and fine-needle aspiration (22 g) was performed in 4 (8%). The median number of samples collected was 4 (range: 2-9). The results were diagnostic in 54 cases (94.7%, 95% confidence interval [CI]: 88.7-100.0). There were 12 (21%, 95% CI: 10.1-31.9) patients with minor complications and 2 (3.5%, 95% CI: 0.0-8.4) with major complications (2 splenic bleeds requiring embolization, no splenectomy, or deaths). No variables (needle size, lesion size, and number of passes) were associated with complication rate. CONCLUSION: Percutaneous image-guided biopsy of the spleen at a single tertiary care institution demonstrates major complication rate comparable to that in the literature with no variables associated with complication rate; there were no cases of splenectomy or death.

After-hours radiology coverage in children's hospitals: a multi-center survey.

BACKGROUND: Although the provision of pediatric emergency and trauma radiology has become increasingly prevalent in North America over the last few years, many hospitals differ in their models of providing after-hours coverage. OBJECTIVE: To describe the scope of after-hours radiology services provided in children's hospitals in North America, and the means by which different radiology departments deliver this coverage. MATERIALS AND METHODS: The Society for Pediatric Radiology Emergency and Trauma Imaging Committee developed a survey that we electronically distributed to a single representative from each of the 79 hospitals represented in the Society of Chiefs of Radiology at Children's Hospitals (SCORCH). RESULTS: Completed questionnaires were submitted between Aug. 2, 2017, and Sept. 29, 2017, by 44/79 (56%) SCORCH representatives. Contemporaneous after-hours interpretation of radiographs (81%), ultrasounds (81%), body CT (79%) and neurologic CT (75%) with preliminary or final reports was common. Coverage was accomplished most commonly by a combination of evening and overnight shifts 17/44 (39%). Eleven of 44 (25%) hospitals used a model in which radiologists rotate working blocks of overnight service followed by blocks off service. Only 2/44 (5%) hospitals exclusively provided pager coverage after hours. Attending pediatric radiologists were assigned to the majority of after-hours shifts 110/175 (63%), but radiology trainees provided interpretations independently for varying periods of time at 19/44 (43%) surveyed hospitals. Incentives to work after hours included the option to work remotely, as well as additional income, time off, and academic time. CONCLUSION: The model for delivering after-hours pediatric radiology coverage varies. Most hospitals, however, provide contemporaneous interpretations of radiographs, US, body CT and neurologic CT. Most institutions use evening shifts to extend coverage later, with many providing subsequent overnight coverage. Although most shifts are staffed by attending pediatric radiologists, radiology trainees commonly interpret studies independently for varying durations of time after hours.

Gallbladder Cancer: Imaging Appearance and Pitfalls in Diagnosis [Formula: see text].

Gallbladder cancer is an uncommon malignancy with an overall poor prognosis. The clinical and imaging presentation of gallbladder cancer often overlaps with benign disease, making diagnosis difficult. Gallbladder cancer is most easily diagnosed on imaging when it presents as a mass replacing the gallbladder. At this stage, the prognosis is usually poor. Recognizing the features of gallbladder cancer early in the disease can enable complete resection and improve prognosis. Recognition of the patterns of wall enhancement on computed tomography can help differentiate gallbladder cancer from benign disease. Gallbladder wall thickening without pericholecystic fluid presenting in an older patient with raised alkaline phosphatase should raise concern regarding gallbladder cancer. Gallbladder polyps in high-risk individuals need close surveillance or surgery as per guidelines. Small gallbladder cancers in the neck can present as biliary dilatation or cholecystitis, and careful examination of this area is needed to assess for lesion. The imaging appearance of gallbladder cancer is reviewed and supported by local institutional data. Features that differentiate it from its common mimics enabling earlier diagnosis are described.

Gender disparity in academic emergency radiology.

OBJECTIVE: This study is intended to better understand how academic productivity and career advancement differs between men and women emergency radiologists in academic practices. MATERIALS AND METHODS: Parameters of academic achievement were measured, including number of citations, number of publications, and h-index, while also collecting information on academic and leadership ranking among emergency radiologists in North America. RESULTS: In emergency radiology, there are significantly fewer women than men (22.2% vs 77.8%). Of these women, the greatest proportion of women held the lower academic rank of assistant professor (95.4%). Female assistant professors had a higher h-index than men at the same rank (4 vs 2), but it was not statistically significantly higher. There was no significant difference between gender and academic (p = 0.089) or leadership (p = 0.586) rankings. CONCLUSION: This study provides further evidence that gender disparity persists in emergency radiology, with women achieving less upward academic career mobility than men, despite better academic productivity in the earlier stages of their careers. The academic productivity of emergency radiologists at the rank of assistant professor is significantly higher for women than men.

Surveillance Software and Prospective Audit and Feedback Rounds Advance Antimicrobial Stewardship at an Acute Care Community Hospital.

Antimicrobial stewardship is a key strategy to facilitate judicious antimicrobial use. Software that can amalgamate prescribing and microbiology information in near real-time reporting and track antimicrobial resistance patterns aids timely interventions. This article examines the impact of a clinical surveillance software used to identify patients for prospective audit and feedback rounds by an antimicrobial stewardship team on antibiotic utilization, patient outcomes and workload efficiencies at an acute care community hospital. Results from a general internal medicine unit show statistically significant reductions in the use of broad-spectrum antibiotics and antibiotic expenditures, with no untoward changes in key clinical and patient safety outcomes.

The role of peltate scales in desiccation tolerance of Pleopeltis polypodioides.

MAIN CONCLUSION: The extreme drought tolerance of the resurrection fern is in part the result of the dorsal scales that assist in water distribution and controlled desiccation. We studied the effect of peltate scales on water uptake and loss of the desiccation-tolerant epiphytic fern Pleopeltis polypodioides using optical and FTIR microscopy and staining with calcofluor, solophenyl flavine7GFE, and Ruthenium Red. We provide information on structure, property, and function of the scales by measuring water uptake and dehydration, contact angles, and metabolic activity. Peltate scales mainly contain cellulose, xylogalactans, and pectin. Water is absorbed from the center of scales, and the overlapping arrangement of scales facilitates surface spreading of water. Intact fronds hydrated fully within 5 h of imbibition of the apical pinna, without scales water uptake stopped after 1 h. Hydration rates via rhizomes followed a longer time course but also improved in the presence of scales. Fronds with and without scales lost half of their water content in 15 or 4 h, respectively. The overall metabolism of rapidly dehydrated fronds was significantly reduced compared with slowly dehydrated fronds. Thus, water management and metabolism of Pleopeltis are dependent on surface properties determined by peltate scales.

Prevalence of Pancreatic Steatosis at a Pediatric Tertiary Care Center.

OBJECTIVES: Pancreatic steatosis in adults has been proposed to be associated with obesity; however, data on pancreatic steatosis in children are lacking. Our study aimed to measure the prevalence of pancreatic steatosis in children and to examine its association with obesity and nonalcoholic fatty liver disease. METHODS: This is a retrospective chart review study of 232 patients 2 to 18 years old who underwent abdominal computed tomographic imaging in the emergency department or inpatient ward within a 1-year time span and from whom demographics, anthropometrics, and medical history were obtained. Our radiologist determined mean Hounsfield unit (HU) measurements for the pancreas, liver, and spleen. A difference of -20 between the pancreas and spleen (psHU) and between the liver and spleen was used to determine fatty infiltration. RESULTS: Of the 232 patients, 11.5% had a psHU less than -20. The prevalence of pancreatic steatosis was more than double among obese children (19%) than that in nonobese groups (8%). There is a significant correlation between the psHU and liver-spleen HU (r = 0.50, P < 0.001). CONCLUSIONS: Pancreatic steatosis was identified in 10% of the study population and is associated with obesity. Also, pancreatic steatosis is significantly associated with nonalcoholic fatty liver disease. This is the first study assessing the prevalence of pancreatic steatosis in children.

TCF/Lef1 activity controls establishment of diverse stem and progenitor cell compartments in mouse epidermis.

Mammalian epidermis consists of the interfollicular epidermis, hair follicles (HFs) and associated sebaceous glands (SGs). It is constantly renewed by stem and progenitor cell populations that have been identified and each compartment features a distinct mechanism of cellular turnover during renewal. The functional relationship between the diverse stem cell (SC) pools is not known and molecular signals regulating the establishment and maintenance of SC compartments are not well understood. Here, we performed lineage tracing experiments to demonstrate that progeny of HF bulge SCs transit through other SC compartments, suggesting a hierarchy of competent multipotent keratinocytes contributing to tissue renewal. The bulge was identified as a bipotent SC compartment that drives both cyclic regeneration of HFs and continuous renewal of SGs. Our data demonstrate that aberrant signalling by TCF/Lef1, transcription factors crucial for bulge SC activation and hair differentiation, results in development of ectopic SGs originating from bulge cells. This process of de novo SG formation is accompanied by the establishment of new progenitor niches. Detailed molecular analysis suggests the recapitulation of steps of tissue morphogenesis.

Effect of Public Reporting on MR Imaging Use for Low Back Pain.

PURPOSE: To determine whether magnetic resonance (MR) imaging examination rates for low back pain before conservative therapy in the Medicare and privately insured populations changed after introduction of a Centers for Medicare & Medicaid Services public reporting initiative. MATERIALS AND METHODS: Institutional review board approval was obtained, with waiver of informed consent. A retrospective study was performed by using fee-for-service claims data from Medicare and a commercial carrier (Blue Cross Blue Shield of Texas [BCBSTX]) for Texas enrollees. OP-8 was calculated, which is a publicly reported measure as of 2009 of the proportion of MR imaging examinations performed for low back pain without history of conservative therapy. For 330 463 MR imaging examinations, OP-8 rates, trends, and regional variation were analyzed for 2008-2011 within different outpatient settings-outpatient hospital department (OHD) and nonhospital outpatient department (NOD)-according to payer. Largest-volume hospitals were also evaluated within the Medicare population. RESULTS: No significant reduction was found in annual OP-8 values for Medicare or BCBSTX (Medicare OHD, 0.35 for 2008 vs 0.36 for 2009 [P = .01]; BCBSTX OHD, 0.42 for 2008 vs 0.44 for 2009 [P = .03]; Medicare NOD, 0.33 for 2008 vs 0.35 for 2009 [P < .0001]; and BCBSTX NOD, 0.43 for 2008 vs 0.42 for 2009[P = .23]). These changes were not sustained during subsequent years in the BCBSTX population, and there were no further changes in Medicare rates. Among hospitals with highest Medicare volumes, those with the highest OP-8 rates in 2008 were associated with the highest decrease in their measure. (The annual change rate was negative for all years, with 2008 as the reference [P < .0001 for 2009-2011].) Hospitals with the lowest OP-8 rates had increases in OP-8 rates, which persisted in following years (P = .006 for 2009, P = .037 for 2010, and P = .004 for 2011). Hospitals with baseline OP-8 rates in the 25th-75th percentile remained relatively steady over time. CONCLUSION: No evidence was found that public reporting (OP-8) reduced MR imaging rates for low back pain without conservative therapy in either Medicare or commercially insured populations in hospital or nonhospital settings.